Radiation Therapy Oncology Group (RTOG), a cooperative association of physicians (radiation, medical and surgical oncologists, pathologists), laboratory scientists (tumor biologists, physicists), and biostatisticians, has been honed to a sharp instrument for clinical trials in cancer treatment in the 2.5 years since its last renewal application. It has recruited new institutions and new leaders. It has sharply reduced accrual to Phase I/II studies emphasizing Phase III trials seeking improved survival. Phase III trials have been, or will soon be completed with inoperable carcinoma of the esophagus, lung, and bladder. Significant improvements in survival in cancer of the cervix and inoperable cancer of the esophagus have been reported. In each of the disease sites studied by RTOG (brain, head & neck, GI, GU, lung) local-regional tumor control is a major issue. New studies confirming the importance of local-regional control in preventing metastasis and increasing survival have led to new strategies to increase total doses with radiation therapy to combine surgical resection with chemotherapy and radiation therapy, and to use chemotherapy and hormone therapy as adjuncts to local-regional treatments while simultaneously attacking distant micrometastasis. Decrease in morbidity by preservation of organ structure and function is second only to improve survival as an aim; studies are underway or planned to spare the bladder, anal canal, distal rectum, and larynx. Assessment of outcomes for minorities in RTOG studies and the addition of the female genital tract as a site are strong moves to address issues for Special Populations. 3D- Conformal Radiation Therapy was added as a new treatment modality joining time/dose, chemical & biological modifiers, intraoperative radiation therapy, systemic radionuclides. Research planning for hyperthermia was discontinued. Exacting quality assurance guidelines are pursued for both standard and new modalities. Chemoprevention of second malignancies tumors based on models derived from RTOG data bases is now a major thrust led by the Medical Oncology Committee. Laboratory studies (cellular and molecular indices of proliferation, assays of inherent radiosensitivity, cell hypoxic fraction) are underway and planned by the Pathology and Tumor Biology Committees to better understand outcomes of specific treatments, and to select patients for more effective therapies in the future. Quality of life studies and late effects assessments, under new committees, complement the emphasis on improving survival and organ preservation. The large data bases and long-term observations available from RTOG studies continue to serve as unique resources to study-specific disease sites. Finally, the marked increase in accrual, after a period of uncertainty with the new reimbursement approach, assures that clinical investigations by RTOG will be completed quickly and that the new results will rapidly be available for planning future studies of cancer treatment.